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Guest post by epidemiologist Daniele Fallin, PhD, of Johns Hopkins Bloomberg School of Public Health

My work focuses on autism and understanding how genes and environments interplay to cause this developmental disorder. Much of this work is funded by federal grants, but there can be gaps in what these grants can support, especially in new fields of research. Support from Autism Speaks has been amazing in helping fill these gaps.

In particular, Autism Speaks provided important support for two of my current projects. The funding is allowing us to study families with autism and, so, gain insights into interactions between autism risk genes and environment exposures.

The Early Autism Risk Longitudinal Investigation (EARLI) is a national study of families that have at least one child on the autism spectrum and anticipate having more children. By following these high-risk families we seek to identify causes and risk factors—be they genetic, environmental or a combination of both. Information is regularly collected from mothers enrolled in the study, and their newborns receive free developmental assessments until 3 years of age.

The second study is a genome-wide investigation of DNA methylation, or epigenetics. It will allow us to investigate how various environmental exposures can affect gene expression in ways that increase—or potentially decrease—the risk of autism. This study will place special focus on environmental exposures during crucial periods of prenatal brain development.

Autism Speaks realizes the importance of these new areas of research and has put forth great effort to ensure we can explore and, hopefully, uncover risk factors for autism that, over the long term, may lead to prevention and improved treatments.

We continue to recruit study participants. Specifically we are enrolling mothers who have one or more children with autism and who may become pregnant or who are currently less than 28 weeks pregnant. They must live near an EARLI research site (California, Maryland or Pennsylvania). For more details, please visit www.EARLIstudy.org or our Facebook page.

On behalf of the EARLI research team, I want to extend a special thanks to Autism Speaks supporters for helping make this pioneering research possible.

Explore more of the studies our supporters are funding with our Grant Search Engine. And read more autism research news and perspective on the science page.

Posted by Autism Speaks Director of Research for Environmental Science, Alycia Halladay, Ph.D.

To date, relatively few scientists are studying autism in China. Clearly the need there is great, for with its population of over a billion, we may be looking at millions of persons affected by autism. With this in mind, Autism Speaks partnered with China’s Fudan University to convene a meeting of leading international experts in autism and children’s health in Shanghai last week.

As part of this visit, I and development psychologist Alice Kau, Ph.D., of the National Institute for Child Health & Human Development, visited Xin Hua Hospital and its recently completed Shanghai Key Lab of Children’s Environmental Health. Both are affiliated Shanghai’s Jiao Tong University School of Medicine.

There we met the lab’s executive director, Jun Jim Zhang, MD, Ph.D., and his colleagues. In recent years, they have been studying how exposure to heavy metals such as mercury and lead affects child development. Environmental lead contamination, a problem largely minimized in the United States, remains a widespread problem in China, owing to unsafe disposal of lead products including waste from lead battery plants.

The Shanghai Key Lab’s affiliation with Xin Hua Hospital allows its scientists to collect blood samples at birth and throughout a child’s development. Their lab is also collecting information on intellectual function and other developmental behaviors. Among their projects is the Shanghai Birth Cohort, which will recruit 100,000 pregnant women from hospitals throughout Shanghai and follow their children throughout adolescence.

To date, the researchers at Shanghai’s Key Lab have been focusing their research on potential environmental causes of childhood asthma, sleep disorders and leukemia. Looking forward, they are keenly interested in expanding their research to include neurodevelopmental issues such as autism.

Thanks to our new collaboration, they will be participating in Autism Speaks Environmental Epidemiology of Autism Research Network. In doing so, they will be sharing their information with autism researchers in North America and elsewhere, even as they receive guidance on screening for autism spectrum disorder (ASD).

Given the unique physical, chemical and psychosocial environment in China, we believe that this collaboration can greatly advance our understanding of the environmental and genetic risk factors that contribute to the development of ASD. We look forward to working with this wonderful research team to help solve the autism puzzle in China, North America, and around the world.

To bring readers up to speed, the above question stems from two reports: In July, a group of California researchers reported a modest increase in the risk that a child would develop autism if his or her mother took selective serotonin uptake inhibitors (SSRIs) during pregnancy. The results were based on a very small sample of children exposed to antidepressants during the time their mothers were pregnant—just 20 children with autism compared to 50 without autism. This past month, another team of scientists reported that rats fed SSRIs as newborn pups exhibited abnormalities in brain development.

Given the great hunger for information about what causes autism, both studies made headlines. Unfortunately, the media stories may have served to alarm without putting these early and inconclusive scientific findings into perspective.

First and foremost, research with animals and investigations looking at a small number of cases are both important for guiding larger, more informative studies. But in and of themselves, these two particular studies don’t come close to reaching the bar at which scientific evidence is reliable enough to warrant a change in behavior. We feel this is particularly true of important medical decisions such as the need to treat depression, which can be a serious and life-threatening illness.

Take, for instance, the small number of children in the California study. This small “sample size” increases the likelihood that the results were due to chance or other unrelated factors. In other words, they may not represent real differences in risk. It is very common in science for such preliminary findings to vanish when researchers repeat the analysis with a larger, more “statistically significant” number of cases.

In addition, among women taking SSRIs, there may be other, hidden factors responsible for raising autism risk among their future children. For example, we know that anxiety is common among persons with an autism spectrum disorder (ASD). In fact, many of those who learn, as adults, that they have an ASD do so when they seek treatment for anxiety and/or related depression. A common type of medicine prescribed in these instances is SSRIs. We also know that ASDs tend to run in families. So it may be that family genetics—not SSRIs—produced the above-mentioned finding of a modest increase in the prevalence of autism among children whose mothers took these antidepressants during pregnancy.

And the rat study? While it’s useful for guiding the focus of further research, we simply can’t extrapolate results from rats to humans.

Finally, we worry about the consequences of women going off antidepressants when they truly need these medications. Certainly if a woman is pregnant or trying to become pregnant, she should discuss all her medicines with her physician—so that with guidance she can weigh the risks and benefits of continuing or discontinuing one or more of them. Certainly, a woman’s untreated depression can itself pose a danger to her pregnancy or newborn child. The bottom line: If you have concerns regarding your medications during pregnancy, discuss them with your physician, who can help you make the best decision for you and your family.

Today’s question came in response to my last blog post. In it, I explained that when scientists talk about the “environmental factors” that increase the risk of a disorder, they’re referring to pretty much any influence beyond genetics.

The commenter’s question is a great one that scientists are actively exploring. The short answer is that inherited genes (DNA) and environmental factors seem to interact to influence whether an infant goes on to develop autism. So if the commenter’s twins are fraternal (meaning they share about half their DNA), the difference in their genetic makeup might explain why only one developed autism.

But what if the boys are identical twins–meaning they share exactly the same DNA? In this case, something beyond genes likely accounts for the different outcomes. Comparing the rates of autism among identical and fraternal twins provides clues.

In July, researchers used our Autism Genetic Resource Exchange (AGRE) to complete the largest autism twin study to date. They found a 70 percent overlap in autism among identical twins and a 35 percent overlap among fraternal twins. That overlap between fraternal twins is much higher than the estimated 19 percent overlap between different-age siblings.

These numbers tell us that it’s not always genes alone that determine whether a child develops autism. If it were, two identical twins would always share the same outcome, and the rate of a shared autism among fraternal twins would look more like that for different-age siblings. So we conclude that shared environmental influences are also at play.

Although twins share very similar pregnancy and birth environments, those environments aren’t exactly the same. For example, twins can have different positions in the womb or different placentas, and this can affect such environmental influences as blood and oxygen flow. Indeed, twins often have different birth weights, a known risk factor for autism.

It’s important to remember that “environmental” influences such as these don’t cause autism by themselves. Rather, if a child has a genetic predisposition for developing autism, these influences may further increase the risk.

Autism Speaks continues to fund and otherwise support research on both genetic and nongenetic risk factors for autism. EARLI is a network of researchers who follow mothers of children with autism beginning at the start of another pregnancy. IBIS is a study of early brain development in the younger siblings of children with autism. These studies depend on the participation and support of the autism community. Please visit our Participate in Research page to learn more.

Importantly, these studies provide insights into the underlying biology of different types of autism. This in turn becomes a basis for developing ways to treat and possibly prevent autism. As always, the goal of the research we support is to improve the lives of all on the autism spectrum.

Research has taught us that there’s no simple explanation for what causes autism. We know that genes play a role, but they aren’t the whole picture. Environment also matters.

However “environment” can be a tricky term, as pediatrician Perri Klass recently noted in her New York Times column. In autism research, we use the word to refer to pretty much any influence beyond inherited genes—not just exposure to pollutants or other toxic chemicals.

Clearly, countless fetuses and babies are exposed to “environmental risk factors” such as these without ever developing autism. But if a child is genetically predisposed to autism, it appears that these influences further increase the risk. For this reason, we say that environmental factors increase the risk of autism rather than cause it.

Research has suggested that many other environmental, or nongenetic, factors may increase the risk for autism. But scientists can’t yet say whether these involve direct (versus coincidental) links. Such factors include a pregnant woman’s exposure to certain chemicals such as pesticides and phthalates (commonly found in plastics) or certain drugs such as terbutaline (used to stop premature labor), valproic acid (to control seizures), and some antipsychotics and mood stabilizers. Of course, in the case of medications, any possible increased risk of autism must be balanced against a woman’s medical needs—which can likewise affect the health of her pregnancy and children.

In addition, most environmental factors associated with autism appear to increase risk only slightly and only in combination with other factors such as genetic predisposition. So it is difficult, in most cases, to pinpoint any one environmental influence. For these reasons, Autism Speaks continues to fund research on a wide range of environmental risk factors. Importantly, the more we learn about how these influences affect brain development, the better we can help the children, adults and families who are affected by autism.

Want to learn more about the research Autism Speaks is funding? On our Science Grant Search page, you can browse studies by topic and location. Finally, if you or your child is affected by autism, please consider participating in one of our clinical studies. Thanks, and please keep sending us your questions.

Last month, a group of California researchers reported an increased risk of autism among babies whose mothers took a certain catergory of antidepressant medications–selective serotonin reuptake inhibitors (SSRIs)—during the first trimester of pregnancy. You may know these drugs by such brand names as Prozac, Effexor, Paxil, and Celexa.

So what do these results mean for pregnant women? First, caution is needed before rushing to judgment. The study was relatively small, and the increase in the risk of autism was modest. So more study is clearly needed to confirm the link and clarify how great a risk, if any, is associated with a mother using this type of antidepressant during pregnancy.

Further caution is needed because the effects of a mother’s anxiety and depression during pregnancy and early infancy are well known. In fact, it’s not clear whether the autism risk associated with taking antidepressants during pregnancy is, in fact, related to the women’s depression rather than the drugs themselves.

For these reason, many doctors have argued that the benefits of SSRIs outweigh concerns about risks that SSRI exposure may pose to a fetus or infant during pregnancy and nursing. Clearly, more research is needed.

Beyond SSRIs, researchers have looked at several other medications to see if their use during pregnancy increases the risk that a baby will go on to develop autism. Among the most thoroughly researched is the anti-seizure medication valproic acid (U.S. brand name Depakote). Studies show that, as a group, children whose mothers take valproic acid during their first trimester of pregnancy are more likely to develop an autism spectrum disorder (ASD) than are children who are not exposed.

Autism Speaks has supported research into how valproic acid might contribute to the development of ASDs. Through the study of donated brain tissue, for example, we have learned that individuals with autism share some “neuropathologies,” or altered brain features, with those who were exposed to valproic acid before birth. In addition, severalstudies show that exposure to valproic acid during critical periods of brain development can produce autism-like behaviors in animal models.

So the good news is that our research has deepened understanding about how valproic acid during pregnancy can contribute to the development of ASDs. The bad news is that it can be quite dangerous for women with epilepsy to stop taking this medication during pregnancy—owing to their increased risk of seizures. As a result, such decisions should be made carefully with a physician can discuss alternative drugs.

Findings are still emerging with other medications given during pregnancy. For instance, relatively small studies (such as this one) suggest an increased risk for ASD in babies whose mothers were given the medication terbutaline to stop premature labor. Another small study suggested increased risk of autism related to women taking high doses of the anti-ulcer drug misoprostol early in pregnancy. (This drug is also used to induce labor later in pregnancy.) But in many cases, such preliminary research has yet to move past the “interesting” stage to reach enough certainty to change medical practices.

Other, larger studies hint at an increased risk of autism in the babies of women who take certain broad classes of medications such as antipsychotics or mood stabilizers during pregnancy. Still the question remains: Is the autism risk due to the medications or to the underlying medical conditions that the drugs are being used to treat?

Beyond medications, studies have revealed a number of other pregnancy complications and events that appear to contribute to the risk that a baby will go on to develop autism. These include the pregnant mother’s exposure to toxic chemicals, infections such as flu, and her diet and nutrition at the time of conception as well as during pregnancy.

Autism Speaks continues to fund a number of important studies looking at autism risk factors during pregnancy. If you have at least one child already diagnosed with an ASD, find out more about participating in the EARLI study (link at left) before or at the start of your next pregnancy. Or consider enrolling your child and family in the CHARGE study, which looks at risk factors before, during, and after your child’s birth.

We will be continuing to update you on the science as it emerges. If you have any concerns about the medications you are taking during pregnancy, please discuss them with your doctor. For more resources, we also recommend the Organization of Teratology Information Specialists.

Posted by Alycia Halladay, PhD, director of research for environmental science, Autism Speaks

For over four decades, autism researchers have been combing through birth records to look for events that might increase the risk that a newborn goes on to develop an autism spectrum disorder (ASD). Many clues have emerged regarding the influence of such factors as prematurity, low birth weight, method of delivery, or even the season in which conception or delivery occurs. But no one study was large enough to provide definitive answers, and inconsistent results between studies have caused confusion among scientists as well as parents trying to follow the science.

Today, the respected journal Pediatrics publishes a study that goes far in cutting through the confusion. Researchers from Harvard and Brown universities reviewed and analyzed the combined results of 40 studies that looked at potential autism risk factors during the birth (perinatal) and newborn (neonatal) period.

Such a “meta-analysis” study is a powerful tool in science, as it allows researchers to combine and compare findings from different sources to get a clearer, more reliable picture of the associations between potential risks and conditions such as autism. Importantly, the study confirmed an association between autism and such conditions as abnormal fetal presentation during delivery (for example, breech), fetal respiratory distress (breathing difficulties), birth injury or trauma, low 5-minute APGAR score (a 1-10 score for assessing newborn health after delivery), newborn seizures, low birth weight, multiple births (twins, triplets, etc.), anemia (low blood iron, and being born in the summer.

Of note, preterm birth was not found to be associated with ASD, of particular interest because there had been considerable differences on this count across earlier studies. Most importantly, perhaps, the researchers concluded that the evidence did not implicate any one perinatal or neonatal factor as causing autism by itself. Rather, the evidence suggests that a combination of these factors—reflecting generally poor conditions during and immediately after birth–may increase the risk that a child with an underlying genetic disposition will develop autism.

One common thread across several of these risk factors is that they result in a lack of adequate blood flow to the brain during the birth process. One hypothesis is that, when combined with a genetic predisposition, oxygen deprivation to the brain worsens abnormal brain development. Studying these and other environmental (versus genetic) risk factors for autism is important to increase our understanding of the biology of ASD and to provide practical guidance for physicians and parents on how to avoid or modify those risk factors that can be changed.

In addition, this meta-analysis strongly suggests that pediatricians and parents should closely monitor the development of babies born in difficult situations so that early intervention can be offered should developmental issues such as autism arise. What this study does not say is that difficult birth means a baby will go on to develop autism. Rather, these conditions and complications may increase the risk of autism among those who have a genetic predisposition for developing it.

As in my last post, I want to invite readers to explore the many environmental risk studies that Autism Speaks is supporting with donor dollars, scientific resources, and the participation of autism families in clinical studies. Please see our Grants Search and Participate gateways at www.autismspeaks.org. Thanks for being a vital part of our mission to improve the lives of all who struggle with autism. For more on the Pediatrics meta-analysis study, also see Autism Speaks news.